This proposal outlines the development of new chemical methods for alkyl-alkyl cross-coupling reactions to form carbon-carbon bonds and application of these methods for synthesis of lead compounds that will be evaluated for anti-cancer activity. The objectives of this project are to generate new strategies for stereospecific cross-coupling reactions, where the stereochemical information from the electrophilic reaction partner is translated to the newly formed stereogenic center of the product. These methods will be utilized in the synthesis of di- and triarylmethane analogs of anti-cancer agents. Collaborative studies to test the activity of these analogues for inhibition of tubulin polymerization, as well a broad screens against several cancer cell lines, will also be performed. This project will directly impact the development of new pharmaceutical agents by providing new strategies for their preparation and validation of the therapeutic potential of the enantioenriched diarylmethane pharmacophore.